tbuckley/cabot-search huggingface dataset:
QOL-32. Patients treated for malignant brain tumor in the first three years of life: clinical sequelae
Authors: Simonetta Giaquinta, Bartolomeo Rossi, Marta Pillon, Elisa Carraro, Alessandra Biffi, Elisabetta Viscardi
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Pediatric Central Nervous System tumors are the most common solid tumors in children with a higher incidence rate in the first years of life. Patients treated for brain tumor are at high risk of sequelae. In the first years of life, brain immaturity increases the risk of developing these complications. OBJECTIVE: The goal of this study was to evaluate the medium and long term sequelae of malignant brain tumor treatment in patients diagnosed in the first three years of life and to correlate these sequelae with tumor histology, localization and treatment. PATIENTS AND METHODS: Forty - nine children with aggressive brain tumor diagnosed in the first three years of life followed in the Pediatric Hematology and Oncology Department of Padua between January 2000 and December 2020 were enrolled in this study. We evaluated features, such as age at onset, tumor localization, neurosurgical resection, histology, treatment and patient outocome. From May to September 2021 we clinically evaluated 16 of them who survived to treatment and we identified the presence of visual impairment, hearing loss, endocrine dysfunctions and neurological deficits in them. RESULTS: The most common sequelae in our patient population is motor impairment (30.8%), followed by endocrine dysfunction (23%), visual impairment (19.2%), epilepsy (11.6%), cranial nerve palsy (7.7%) and hearing loss (7.7%). In this study epilepsy is significantly associated with supratentorial tumors and endocrine dysfunction with high dose chemotherapy. CONCLUSIONS: Our data and recent literature confirm the high incidence of tumor and treatment sequelae in these patients. Therefore, since diagnosis, a multidisciplinary evaluation and management are necessary for improving patients’ prognosis.
The association of COVID-19 testing with cancer care disruption.
Authors: John Panzone, Christopher Welch, Maximillian S Wu, Joseph M Jacob, Oleg Shapiro, Alina Basnet, Gennady Bratslavsky, Hanan Goldberg
Journal: Journal of Clinical Oncology (2022)

e18558 Background: Research has shown that the COVID-19 pandemic has reduced access to cancer treatment and care for patients, especially for COVID-19 patients. Methods: We investigated the impact of COVID-19 testing on access to cancer care. A US based cross sectional study was conducted on 2,393 cancer patients using data from the 2020 National Health Interview Survey. Multivariable logistic regression was used to assess associations between COVID-19 testing and likelihood of receiving cancer treatment or other cancer care during the pandemic. Results: Patients who reported ever being tested for COVID were on average younger (66.9 vs 69.3, p&lt;0.001). Patients with professional school education reported higher rates of being tested than lower education levels (40.0%, p=0.032). Tested patients reported higher rates of not receiving medical care due to COVID-19 (23.3% vs. 19.1%, p=0.026). On multivariable analysis, patients who reported ever being tested for COVID-19 were less likely to receive cancer treatment (OR 0.639, 95% CI 0.489-0.834, p=0.001) or receive any other cancer medical care (OR 0.657, 95% CI 0.523-0.825, p&lt;0.001) (Table). Conclusions: These data suggest COVID testing itself is associated with increased likelihood of cancer care disruption. As the pandemic persists, awareness of cancer care disruption, even by testing alone, should be raised.[Table: see text]
EPID-03. Epidemiology, treatment and outcomes of children and young adults with CNS tumors in Armenia
Authors: Julieta Hoveyan, Henrik Grigoryan, Shushan Hovsepyan, Anna Avagyan, Eduard Asatryan, Gevorg Tamamyan, Ruzanna Papyan, Lilit Sargsyan, Lusine Hakobyan, Samvel Bardakhchyan
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: CNS tumors are the most common solid tumors in children and the leading cause of cancer related deaths. The incidence of CNS tumors is 1.7-6.21 cases per 100000 children. The aim of current study is to analyze epidemiological data, treatment and outcomes of children and young adults (&amp;lt;25 years) with CNS tumors in Armenia during last 25 years. METHODS: We have collected data of pediatric and young adult patients treated in neurosurgery department, three major chemotherapy clinics and radiation therapy department from 01.01.1995 to 31.12.2020 in Armenia. Incidence by gender, age at diagnosis, the time from first complaints to diagnosis, histopathology results and overall survival rates were calculated. RESULTS: The population-based data revealed 176 patients diagnosed with primary CNS tumors during 25 years. Among them 98 (55.7%) were males. Mean age at diagnosis was 7.07 years and the mean time from the first complaints to diagnosis was 6.55 months. Medulloblastomas and other embryonal tumors (26.7%), low grade gliomas (16.5%), retinoblastomas (12.5%) and high grade gliomas (10.8%) were the most common diagnosed malignancies. Craniopharyngiomas, germ cell tumors and other malignancies were observed in 9.1% of patients. For 24.4% histopathological data was missing. Surgery, chemotherapy and radiation therapy were performed in Armenia for 62.5%, 33.5% and 19.3% patients respectively. Follow up information was available for 119 (67.6%) patients. 5-year overall survival was 76%. CONCLUSION: Embryonal tumors and gliomas were the most common diagnosed CNS malignancies in Armenia which is consistent with international data. Multimodal treatment was often not available in Armenia during study period, especially for early cases. We hope recent advances in surgery, chemotherapy, and radiotherapy will help to improve treatment outcomes.
Geriatric assessment as a predictor of survival among older Indian patients with cancer.
Authors: Abhijith Rajaram Rao, Anant Ramaswamy, Sharath Kumar, Shreya Gattani, Ratan Dhekale, Jyoti Krishnamurthy, Sarika Mahajan, Anuradha Daptardar, Jayita Deodhar, Manjunath Nookala, Supriya Goud, Sucheta More, Dipti Nakti, Chetan Mudliya, Nandini Sharrel Menon, Vijay Maruti Patil, Vikram Gota, Shripad Dinanath Banavali, Kumar Prabhash, Vanita Noronha
Journal: Journal of Clinical Oncology (2022)

e24012 Background: ASCO guidelines recommend that geriatric assessment (GA) should be performed in all older adults with cancer. However, GA is labor- and time-intensive, hence the uptake is poor, especially in crowded resource poor-settings. There are no data correlating GA with overall survival (OS) outcomes from the Indian subcontinent. Methods: A prospective observational study in the geriatric oncology clinic of the Tata Memorial Hospital in Mumbai, India. Patients aged 60 years and above, with cancer who underwent a GA were enrolled. The domains assessed included: function (basic and instrumental activities of daily living, timed-up-and-go), nutrition (body mass index, unintentional weight loss, mini-nutritional assessment), comorbidities, cognition, psychological (depression, anxiety), social support, and medication (polypharmacy and potentially inappropriate medications). Patients with &gt; 2 deranged GA domains were considered frail. Results: Between June 2018 and January 2022, 909 patients were enrolled. The median age was 69 (IQR, 60-88) years. Common malignancies included lung (40%), esophagus (21%) and head and neck (11%); 53% had metastatic disease. 80% had &gt; 2 impaired domains in GA patients had vulnerabilities in a median of 3 (IQR, 0-5) domains. Median OS in fit patients based on the GA was 17.5 (95% CI, 13.9-21.0) months vs 12.1 (95% CI, 10.1-14.0) months in frail patients, (HR 0.66; 95% CI, 0.49-0.88, p = 0.005), which remained significant after adjusting for age, sex, and stage (HR, 0.71; 95% CI: 0.53-0.94, p = 0.021). In the multivariate analysis (Table), the domains that were predictive of survival were nutrition (HR: 0.65, 95% CI: 0.47-0.92, p = 0.014), cognition (HR: 0.65; 95% CI: 0.46-0.91, p = 0.012) and fatigue (HR: 0.74, 95% CI: 0.56-0.98, p = 0.038). Conclusions: In older Indian patients with cancer, GA is a powerful prognosticator of survival. In settings where a complete GA is not possible, nutrition, cognition, and fatigue should be the minimum domains assessed. Clinical trial information: CTRI/2020/04/024675. [Table: see text]
LINC-24. Survival and genetic evaluation of patients diagnosed with choroid plexus tumor treated at a Brazilian institution
Authors: Milena Oliveira, Nasjla Silva, Andrea Cappellano, Jessica Rodrigues, Daniela Almeida, Sergio Cavalheiro, Patricia Dastoli, Frederico Silva, Maria Teresa Seixas, Fernanda Lima
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Choroid plexus tumors (CPT) are rare intraventricular neoplasms of epithelial origin. They usually occur in the 2nd year of life, corresponding to 0.4-0.6% of intracranial tumors in this age group. They are classified, according to WHO 2021: choroid plexus carcinoma (CPC), atypical choroid plexus papilloma (ACPP) and choroid plexus papilloma (CPP). Li-Fraumeni syndrome (LFS) is present in 50% of patients with CPC. In Brazil, the TP53p.R337H mutation affects 0.3% of the population in the South/Southeast. OBJECTIVE: Evaluate the genetic assessment and overall-survival (OS) of patients with CPT treated at IOP/GRAACC/UNIFESP. PATIENTS/METHODS: Between 1995-2021, 48 patients were diagnosed with CPT in our institution, 27 CPC, 18 CPP and 3 ACPP. From 2012-2021 patients were referred for genetic evaluation, 16 of which had CPC (2 had previously CPP). Family history for neoplasms was present in 87.5%, 37.5% compatible with Li-Fraumeni Syndrome (LFS) of which 50% with positive mutations. The molecular investigation of TP53 gene in patients with CPC was performed and positive in 62,5%:R337H(6 patients), R110C*, R158H*, H179R*, R196* (*1 patient each). For those with R337H, p53 protein immunohistochemistry resulted in 90-100% positivity. Treatment strategies consisted of surgery with gross total resection being achieve in all ACPP, 94,4% CPP and 55,5% CPC. Chemotherapy was performed in only 1 case of ACPP and all CPC with a variety of schemas, including high dose of chemotherapy and autologous bone marrow transplant for slow responders or recurrent disease. The three- and five-years OS for CPC was 72.5% and 61.7%, respectively. For CPP and ACPP 5y OS was 100%. CONCLUSION: The present study is in agreement with the literature showing an excellent survival for CPP and ACPP but an inferior outcome for patients with CPC and TP53 mutation despite being assisted by a well-prepared multidisciplinary team with an adequate treatment.
A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects
Authors: Dake Hao, Ruiwu Liu, Tomas Gonzalez Fernandez, Christopher Pivetti, Jordan Elizabeth Jackson, Edwin Samuel Kulubya, Hong-Jiang Jiang, Hai-Yang Ju, Wen-Liang Liu, Alyssa Panitch, Kit S. Lam, J. Kent Leach, Diana L. Farmer, Aijun Wang
Journal: Bioactive Materials (2022)

Significant progress has been made in designing bone materials capable of directing endogenous cells to promote vascularized bone regeneration. However, current strategies lack regulation of the specific endogenous cell populations for vascularized bone regeneration, thus leading to adverse tissue formation and decreased regenerative efficiency. Here, we engineered a biomaterial to regulate endogenous cell adhesion and promote vascularized bone regeneration. The biomaterial works by presenting two synthetic ligands, LLP2A and LXW7, explicitly targeting integrins α4β1 and αvβ3, respectively, expressed on the surfaces of the cells related to bone formation and vascularization, such as mesenchymal stem cells (MSCs), osteoblasts, endothelial progenitor cells (EPCs), and endothelial cells (ECs). In vitro, the LLP2A/LXW7 modified biomaterial improved the adhesion of MSCs, osteoblasts, EPCs, and ECs via integrin α4β1 and αvβ3, respectively. In an adult rat calvarial bone defect model, the LLP2A/LXW7 modified biomaterial enhanced bone formation and vascularization by synergistically regulating endogenous cells with osteogenic and angiogenic potentials, such as DLX5+ cells, osteocalcin+ cells, CD34+/CD45- cells and CD31+ cells. In a fetal sheep spinal bone defect model, the LLP2A/LXW7 modified biomaterial augmented bone formation and vascularization without any adverse effects. This innovative biomaterial offers an off-the-shelf, easy-to-use, and biologically safe product suitable for vascularized bone regeneration in both fetal and adult disease environments.
Lenvatinib combined with hepatic arterial infusion of modified FOLFOX regime as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria.
Authors: Feng Shi, Qicong Mai, Meng Chen, Chunlin Li, Xiaoming Chen
Journal: Journal of Clinical Oncology (2022)

e16154 Background: Transcatheter arterial chemoembolization (TACE) is not effective for intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria (substage B2) and also impairs the hepatic functional reserve, resulting in poor prognosis. This study aimed to investigate the efficacy and safety of lenvatinib combined transarterial infusion chemotherapy with FOLFOX regimen (FOLFOX-HAIC) for substage B2 HCC. Methods: This study retrospectively enrolled and analyzed 18 patients with substage B2 HCC from Nov. 2019 to Nov. 2021. Patients were orally administered with 8 mg(≤60kg) or 12mg(&gt; 60kg) lenvatinib once daily initially, and FOLFOX-HAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m 2 on day 1, and fluorouracil infusion 2,400 mg/m 2 for 46 hours) was performed every 3 weeks and up to 6 sessions. Then patients were treated with lenvatinib alone. Patients with downsizing HCC was allowed for potential curative therapies (surgical resection or ablation). Best response according to the RECIST 1.1 and mRECIST criteria, progression-free survival (PFS) and treatment-related adverse events (TRAE) were evaluated. Results: 18 patients (median age: 63.0 years) underwent a total of 77 cycles of HAIC therapy (mean: 4.3; range: 2-6). All patients were classified as Child-Pugh A class. The ORR were 83.3% (RECIST 1.1) and 94.4% (mRECIST), the disease control rate (DCR) was 100% (RECIST1.1/mRECIST). With a median follow-up period of 12.9 months, the median PFS was 10 months. During the follow-up period, no patient died, and 8 of 18 (44.4%) patients experienced progression. 6-, 9-, and 12-months PFS rates were 94%, 74%, and 55%, respectively. TRAE occurred in 15 of 18 patients (83.3%). Two grade 3 TRAE (hepatic encephalopathy and hypertension) was observed. Conclusions: Lenvatinib combined with FOLFOX-HAIC was well tolerated and had shown promising ORR, PFS rates in patients with intermediate-stage HCC beyond up-to-seven criteria. A prospective large-scale trial is needed to justify these results. [Table: see text]
Spatiotemporal multiomic landscape of human medulloblastoma at single cell resolution.
Authors: Hailong Liu, Tao Jiang, Xiaoguang Qiu
Journal: Journal of Clinical Oncology (2022)

2069 Background: Medulloblastoma is the most common malignant childhood tumor type with distinct molecular subgroups. While advances in the comprehensive treatment have been made, the mortality in the high-risk group is still very high, driven by an incomplete understanding of cellular diversity. Methods: We use single-nucleus RNA expression, chromatin accessibility and spatial transcriptomic profiling to generate an integrative multi-omic map in 40 human medulloblastomas spanning all molecular subgroups and human postnatal cerebella, which is supplemented by the bulk whole genome and RNA sequences across 300 cases. Results: This approach provides spatially resolved insights into the medulloblastoma and cerebellum transcriptome and epigenome with identification of distinct cell-type in the tumor microenvironment. Medulloblastoma exhibited three tumor subpopulations including the quiescent, the differentiated, and a stem-like (proliferating) population unique to cancer, which localized to an immunosuppressive-vascular niche. We identified and validated mechanisms of stem-like to differentiated process among the malignant cells that drive tumor progression. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing stem-like malignant cells as a hub for intercellular communication. Multiple features of potential immunosuppression and angiogenesis were observed, including Treg cells and endothelial cells co-localization in compartmentalized tumor stroma. Conclusions: Our study provides an integrative molecular landscape of human medulloblastoma and represents a reference to advance mechanistic and therapeutic studies of pediatric neuro-oncological disease.
Factors associated with recurrence in oral cavity squamous cell carcinoma: A real-world experience from an Indian comprehensive cancer center.
Authors: Siddharth Sood, Prashant Mehta, Sakshi Sharma, Amit Badola
Journal: Journal of Clinical Oncology (2022)

e18018 Background: Oral cavity squamous cell carcinoma (OCSCC) is the third most common malignancies in India with an estimated 72,000 deaths annually. The incidence is increasing owing to rising alcohol and tobacco consumption in last 2 decades. Methods: We performed a retrospective cohort study in patients with OCSCC to identify risk factors for local and metastatic recurrences following definitive treatment including surgery and/or radiation therapy or chemotherapy or both at our institute. Patient records were screened from 2016 till 2021. Eligible patients were followed up for disease status and outcome. Data included sociodemographic details, substance use, tumor differentiation, stage at diagnosis, LVI, PNI, margin status, treatment details and site of recurrence. All statistical analysis was performed on Microsoft excel 2016 and Jamovi version 1.6.23.0. Results: Out of 195 patients files screened, 90 were available for analysis. Demographic details, substance use pattern and tumor profile are highlighted in table. Tongue was the most frequent site involved and most of the tumors were well to moderately differentiated. Majority of the patients presented as locally advanced disease (Stage IVa). LVI and PNI were identified in 5.75% and 29.89% patients respectively while one of the patients had a positive margin after resection. Surgery followed by adjuvant chemo-radiation was the most frequently prescribed treatment (n = 46; 52.8%) whereas 27.59% patients (n = 24) underwent surgery alone. Fifty six (63.3%) patients experienced recurrence out of which 50% were local and 35% were metastatic recurrences. On multivariate analysis, the predictors of disease recurrence were male gender (OR- 3.2; 95% CI- 1.02-10.05; p-0.05), tobacco and alcohol use (OR- 1.93; 95% CI- 0.8-4.6; p- 0.14 and OR- 2.16; 95% CI- 0.82-5.65; p- 0.12 respectively), Stage IVb disease (OR- &gt; 10; 95% CI- 0-10; p-1.0), presence of PNI (OR- 1.39 ; 95% CI- 0.55-3.70; p-0.497) and presence of LVI (OR- 2.54; 95% CI- 0.36-50.8; p- 0.414). Median disease free survival and overall survival of the cohort was 11.3 months and 15 months respectively. Advanced stage, tobacco consumption, presence of LVI and PNI negatively affected overall survival in our cohort. Conclusions: Oral cavity squamous cell carcinoma is among the most preventable malignancies and they contribute to significant morbidity and mortality. This study highlights the role of early detection and management of such patients. Patients may still experience disease recurrence after initial management which may be difficult to treat. Such patients should be encouraged to participate in a clinical trial as treatment options for recurrent disease are limited.[Table: see text]
MODL-13. Patient-derived organoids for modeling pediatric brain tumors
Authors: Chiara Lago, Claudio Ballabio, Evelina Miele, Luca Tiberi
Journal: Neuro-Oncology (2022)

Abstract Central nervous system (CNS) tumors are the most common solid tumors in the pediatric population and the main cause of death among childhood cancers. They present common features related to the development and produce symptoms based on the age of the child, their location and rate of tumor growth. Tumors of embryonal origin, such as medulloblastoma or primitive neuroectodermal tumor, have a higher incidence in younger patients, whereas older ones tend to present tumors of glial origin. Most of CNS-embryonal tumors are highly malignant and consequently leading to poor prognoses. Despite the understanding of the underlying molecular landscape of these tumors that has helped in clinical advances to improve life expectancies of the patients, there is still an emerging need to minimize morbidity and manage the long-term therapy effects. Developing new models to better understand the heterogeneity of these tumors and to test personalized treatment strategies remains a clinical challenge. We are willing to answer to this medical need with Patient-Derived Organoids (PDOs) established through the direct in vitro culture of primary tumors and patient derived xenograft (PDX)-derived tumors. We developed a method for generating PDOs from a variety of pediatric brain cancers that recapitulates the cellular heterogeneity, histological features and mutational profiles of the corresponding parental tumors, also confirmed by the DNA methylation profile analysis, nowadays used for an accurate routine CNS tumors diagnosis. Through this new model, we confirmed the action of some clinically used drugs, obtaining a proof of concept of their possible application as a reliable tool for drug screening. Further applications derive from the enrichment of PDOs culture media for possible tumor-specific antigens that could be useful to define tumor markers identifiable with diagnostic tests or as candidates for new therapies.
HGG-15. Generation of a novel mouse model for brain tumors of the DNA methylation class “GBM MYCN”
Authors: Melanie Schoof, Shweta Godbole, Carolin Walter, Matthias Dottermusch, Thomas Albert, Annika Ballast, Carolin Göbel, Sina Neyazi, Dörthe Holdhof, Catena Kresbach, Mirjam Blattner-Johnson, Franziska Modemann, Ann-Kristin Afflerbach, Alicia Eckhardt, Nina Struve, David Jones, Kornelius Kerl, Julia E Neumann, Ulrich Schüller
Journal: Neuro-Oncology (2022)

Abstract Multiple recent publications have described a highly aggressive subgroup of pediatric glioblastoma, which is clearly separable from other pediatric and adult glioblastoma based on its DNA methylation profile (GBM MYCN). These tumors almost exclusively occur in children and have a median overall survival of only 14 months. Many tumors in this group are driven by MYCN amplifications and harbor TP53 mutations. Otherwise, information about these tumors are still sparse and treatment is ineffective and causes severe side effects in many cases. In order to further investigate the biology and treatment options of these tumors, preclinical models are urgently needed. Here, we describe the generation of hGFAP-cre::TP53Fl/Fl::lsl-MYCN mice, which carry a loss of TP53 and show aberrant MYCN expression in neural precursors of the central nervous system. These animals develop large forebrain tumors within the first 80 days of life with 100 % penetrance. These tumors resemble human GBM MYCN tumors by histology, global gene expression, and DNA methylation. In order to understand the developmental biology and intratumoral heterogeneity, we employed single cell RNA sequencing (scRNAseq) to the murine tumors with first results indicating a resemblance of tumor cells to committed oligodendrocyte precursors. We further show that both murine and human tumor cells are sensitive to AURKA inhibition in vitro, suggesting a potential new therapeutic option for improved patient care. We believe that further characterization and utilization of the model will pave the way to improved treatment strategies for patients with these highly aggressive tumors.